Syndax Pharmaceuticals, Inc.

Thank you for standing by, and welcome to the CINDAC's first quarter 2021 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. To ask a question during the session, you'll need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Melissa Forrest of Argo Partners. Please go ahead.

Thank you. Welcome and thank you to those of you joining us on the line and the webcast this afternoon for a review of syntax's first quarter 2021 financial and operating results. With me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison, Chief Executive Officer, Daphne Caritas, Chief Financial Officer. Also joining us on the call today for the question and answer session will be Michael Metzger, President and Chief Operating Officer, Dr. Michael Myers, Chief Medical Officer, and Dr. Peter Ordentlich, Chief Scientific Officer. This call is being accompanied by a slide deck that has been posted on the company's website, so I'd ask everyone to please turn to forward-looking statements on slide two. Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meeting of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors. This includes those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements represent our views as of today, May 11th, 2021 only. A replay of this call will be available on the company's website following the conclusion of the call. And with that, I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer of Syndex.

Great. Thank you so much, Melissa, and thank you to everyone for joining us on today's call in the webcast. Slide three provides a high-level summary of our current corporate priorities as we strive to realize a future in which people with cancer live longer and better than ever before. We've continued to make great progress in both our clinical programs during the first quarter of this year. We reported the initial data from the phase one trial of SNDX5613, our selective Mennon inhibitor, and are on track to begin potential registration cohorts in that program shortly. In addition, we have completed enrollment of 23 chronic graft-versus-host disease patients on axotilumab at one milligram per kilogram in our Phase II expansion cohort, and enrollment is ongoing in our pivotal Agave 201 trial. We therefore remain on track to have two registrational programs ongoing this year for two first-in-class and potentially best-in-class medicines for two areas of important unmet medical need. Thanks to the support of our many committed investors, we are well financed to vigorously pursue both of our existing programs and to aggressively look for additional opportunities to bring targeted oncology drugs into our pipeline. Let's now turn to slide four in our recent data disclosure of our phase one trial of 5613, our selective menin inhibitor for the treatment of acute leukemia. As we noted in our recent data disclosure, in our phase one trial, 5613 has been well tolerated over multiple cycles with no patient discontinuing for a drug-related adverse event. Our pharmacodynamic data confirms the mechanism of action, and perhaps most importantly, we have a candidate recommended phase two dose that meets all of our pre-specified criteria. We are, of course, excited to have also observed clear evidence of monotherapy activity in this population of patients with relapsed or refractory acute leukemia with both MLLR and NPM1C mutations, with most responses being MRD negative. I want to reinforce why we are so excited about what we are seeing and provide additional data that further builds our confidence in our program. Let me first remind everyone that this is a phase one trial. Patients have received on average three prior therapies. About 40% had relapsed after a bone marrow transplant. a very negative prognostic sign, and almost 60% had previously received venetoclax. These are very difficult to treat patients, and we were delighted to see a 48% overall response rate and 67% of the responses being MRD negative. Every physician currently treating acute leukemia who has reviewed this data with us has been excited by the efficacy we are seeing. And the data has only gotten better over the past weeks with two patients converting to CR with full count recovery. We had pointed out that it is not uncommon for patients with complete eradication of leukemia to initially have incomplete recovery of their additional blood counts. Full recovery can take time. Slide five is a reprise of one of the vignettes we presented at our data disclosure event. You will see here a patient with refractory NPM1C acute leukemia who was treated at our recommended phase two dose and had a rapid MRD negative CR. Initially, however, her blood counts had not recovered to normal and she had a CRI, which is an MRD negative complete response with incomplete recovery of her blood counts. But you can also see that over time, her blood counts fully recovered She had an MRD negative CR with full count recovery and went on to potentially curative bone marrow transplant. At the time of our data disclosure, we noted that five patients had already achieved either a CR or a CRH and that there were five patients still ongoing who had an MRD negative CR but had not yet achieved a CR or CRH. We anticipated that some of those patients would have full count recovery over time, and that's exactly what we have seen. Over the ensuing weeks, two of the patients who had an MRD negative CR but had not yet achieved a CR or CRH have now had full count recovery and now have achieved a CR and remain on study. A third patient of the five who had an MRD negative CR but had not yet achieved a CR or CRH, has improved from a CRI to a CRP, and also remains on study. Of the two remaining patients, one remains on study with a response of CRP, and one is off study due to progressive disease. Slide six shows the response data we presented on April 20th, as well as the updated data as of last Friday. Let me repeat that these data on slide six are from our ongoing phase one trial. This data on slide six is a snapshot in time and the data may further improve. There are still two patients on trial who have had an MRD negative CR but have not yet achieved a CR or CRH. We are looking carefully at the patient characteristics with respect to any potentially appropriate adjustments to our enrollment criteria in our upcoming phase two study. we understand the regulatory precedent for the efficacy hurdle for the approval of 5613 in relapsed and refractory acute leukemia. While there are no guidelines on a specific rate that is required for approval, we have pointed out the rates that were reported for recently approved FLT3 and IDH inhibitors that suggest the CR plus CRH rate above 20% has been acceptable to the FDA. The Phase 1 data that we've generated from our ongoing Augment 101 trial, and again, I want to emphasize it is our data that gives us confidence that 5613 will achieve that level of efficacy in our upcoming Phase 2 trial. I also want to provide a broader context about what we are seeing in the NPM1 population, as we believe it's quite informative and supports our confidence that the efficacy in the NPM1 population should mirror that of the MLLR population. For the avoidance of doubt, we reported that we had treated seven relapsed or refractory patients with NPM1C acute leukemia, and there were two patients with a CR. Of the remaining five patients, one progressed quite rapidly on the third day of treatment, and two had clear evidence of anti-leukemic activity, but unfortunately succumbed to a systemic infection one of the feared complications of acute leukemia prior to attaining a bone marrow response. So we believe the fatality of our clinical data suggests therefore that as predicted from the preclinical data, 5613 will have good activity in patients with NPM1C acute leukemia as well. Slide seven shows our go forward plans for 5613. We anticipate initiating phase two at the end of this quarter. and holding our end of phase one meeting with FDA shortly thereafter. We also anticipate a further update of the Augment 101 data at the end of this year, and we'll of course also look for additional opportunities to provide meaningful updates as events allow. The phase two portion of the trial will enroll three distinct expansion cohorts, patients with MLLR acute lymphoid leukemia, ALL, patients with MLLR acute myeloid leukemia, AML, and patients with NPM1 mutant AML. The Phase 2 portion will enroll both pediatric and adult patients, thereby providing us a potential path to regulatory approval with a broad label including both adults and pediatrics. I should note that the results are positive. This Phase 2 portion of Augment 101 could potentially support a regulatory filing given existing regulatory precedents. We do not yet have a final endorsement of our phase two sample size, nor have we finalized our enrollment rate, and yet it is possible that we could have top line data for one or more of the cohorts sometime next year. Over the last period, we've also been conducting extensive research into the broad landscape of clinical opportunities for 5613 beyond the initial approval in relapsed refractory acute leukemias as illustrated on slide eight. We are not in a position today to lay out the specific next steps in building out the 5613 franchise. I can say that we are using this ongoing analysis to inform specific combination regimens that we anticipate starting to study later this year. Several investigators and leading companies have already reached out to us with novel, exciting ideas for future development of 5613, and we are evaluating those opportunities. Let me now turn to slide nine and axotilamab, our potentially best-in-class monoclonal antibody targeting the CSF1 receptor. As you know, we presented our phase one chronic graft-versus-host disease data at ASH in December of last year. You may recall that we had opened a phase two expansion cohort at the one milligram per kilogram dose, and we are pleased to announce that that cohort has now been fully enrolled. We anticipate presenting later this year the full updated data from both 17 patients from the Phase 1 portion of the trial, as well as the 23 patients enrolled in the Phase 2 expansion cohort at the 1 mg per kg dose. I should emphasize that our base assumption is that this 1 mg per kg dose will be our labeled dose, and hence the Phase 2 expansion cohort is quite relevant as a de-risking event to the eventual outcome of our pivotal trial. Slide 10 outlines our pivotal trial for axotilamab, a chronic graft-versus-host disease. This trial is the axotilamab for graft-versus-host disease trial called Agave 201. This trial is enrolling patients with chronic graft-versus-host disease whose disease has progressed after two prior therapies. Patients must be at least six years of age and have met overall entry criteria. This is a pivotal dose-ranging trial in which patients will be randomized to one of three treatment groups, each investigating a distinct dose of axotilamab given either every two weeks or every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for chronic graft-versus-host disease. Secondary endpoints will include duration of response and validated quality of life assessments using the Leigh symptom scale. Enrollment to the study is underway, and we are on track to deliver top-line data in 2023. We believe that chronic graft-versus-host disease represents a high unmet medical need and an important commercial opportunity, with approximately 14,000 patients suffering from chronic graft-versus-host disease in the U.S. today. With the recent positive pivotal results from both Insights Jackify and CADMINS KD025, we may soon see regulatory approvals and commercial launches that will begin to delineate the commercial opportunity in chronic graft-versus-host disease. Despite recent advancements in this area, to our knowledge, axotelimab is the only agent in clinical development that specifically targets the monocyte macrophage lineage. We believe the data generated to date with axotilumab suggests that it has the potential to play an important role in the treatment of chronic graft-versus-host disease, both as monotherapy and given its safety profile, potentially in combination with complementary medicines. We've also been working extensively with experts in the field of fibrotic disease, and have found a strong consensus that the scientific rationale for the efficacy of axotilumab in chronic graft-versus-host disease firmly supports its potential in a wide variety of fibrotic diseases, such as idiopathic pulmonary fibrosis and scleroderma. We are actively evaluating options by which to build the axotilamide franchise beyond chronic graft-versus-host disease and take advantage of what we believe are a significant set of opportunities that could materially enhance shareholder value. As we have previously communicated, we obtained orphan drug designation from the FDA for the use of axotilamide in IPS. Finally, slide 11 summarizes the transactions that led to the acquisition of the MEDIN MLR program and the Axotilamab program. We believe that we will be able to continue to expand our pipeline through the acquisition or in-licensing of quality, differentiated assets. We believe that we have the necessary skills to evaluate and identify high-quality assets and the clinical development experience to bring these compounds through valuable inflection points. We expect to remain among preferred partners of such transactions. I will now turn the call over to Daphne to review our financial results.